Amplification ofcyclin D1andMDM-2in oesophageal carcinoma

Aims:This study investigated amplification of thecyclin D1andMDM-2genes, and overexpression of the cyclin D1 gene product, in oesophageal carcinoma.Methods:Paired tumour and normal DNA samples from 26 oesophageal adenocarcinomas and 19 squamous cell carcinomas were analysed by Southern blotting with specific DNA probes forcyclin D1andMDM-2, and for a control gene (α-lactalbumin). Thecyclin D1andMDM-2gene copy numbers were calculated for each tumour. Expression of thecyclin D1gene was assessed by immunohistochemical analysis of its protein product.Results:Cyclin D1 gene amplification (by a factor of between two and six) was identified in seven tumours (16%).MDM-2gene amplification (by a factor of between two and 11) was identified in 10 tumours (22%). Overexpression of cyclin D1 protein was identified in eight tumours and was significantly associated with gene amplification (P=0.04; Fisherʹs exact test), and with early T stage (P=0.01; Fisherʹs exact test).Conclusions:Cyclin D1 andMDM-2amplification and cyclin D1 overexpression occur, although infrequently, in the development of oesophageal carcinoma. Cyclin D1 overexpression may influence tumour behaviour, causing the disease to present at an earlier T stage. The mechanism for this effect is unclear, and warrants further investigation.